Commonest cause is iatrogenic;
All glucocorticoids suppress ACTH -> ACTH, and serum cortisol will be low in iatrogenic cushing's syndrome.
The diagnosis of Cushing syndrome is established when at least two different first-line tests are unequivocally abnormal, and physiologic hypercortisolism has been excluded
If a patients has feature of Chushing's syndrome
bedtime salivary cortisol
24 hour urinary free cortisol - Measures the total daily cortisol production without being affected by the cyclical variations in it's production.
Low dose DST
For bedtime salivary cortisol and UFC, two abnormal tests are required.
If cortisol is found to be elevated with the above preliminary tests, next step is to exclude physiologic hypercortisolism.
AKA - pseudo Cushing syndrome.
Clinically, these patients usually do not have skin or muscle manifestations of Cushing Syndrome.
Causes of pseudo-cushing syndrome (i.e causes of elevated cortisol)
Because of various nuances, the above tests must be unequivocally elevated in order to diagnose Cushing's syndrome. Mild elevations are unlikely to indicate Cushing's syndrome.
Once hypercortisolism has been identified and physiologic hypercortisolism as been excluded, the cause of hypercortisolism must be determined.
First step is determining if the cortisol hypersecretion is
ACTH dependent or ACTH independent.
This is done by measuring ACTH levels.
Because of cyclical variations, testing at two different times is recommended.
ACTH < 5pg/ML = ACTH independent hypercortisolism
ACTH > 20pg/mL = ACTH dependent hypercortisolism.
ACTH dependent Hypercortisolism
A mass > 6mm in size in the sella turcica supports a diagnosis of Cushing's disease.
10% of healthy people have masses <6mm in size.
Sampling the ACTH level from the petrosal sinus can be used if the diagnosis is uncertain.
Gastric cancer has poor prognosis and new treatment modalities are needed.
Pathogenesis:
Gastrin, produced by G cells of the antral glands promote growth of gastric adenocarcinoma through cholecystokinin-B receotors which are over expressed in this cancer.
Serum gastrin levels may be increased secondary to
1. chronic administration of proton pump inhibitors,
2. atrophic gastritis,
3. Helicobacter pylori infection,
4. or from de novo gastrin expression from the gastric cancer epithelial cells
[[Hormone Physiology]]
In adults, bone mets are far more common than primary bone tumours.
Bone is the 3rd commonest site of metastatis next to Lung and liver.
Prostate and breast cancer (BC) are responsible for the majority of the skeletal metastases (up to 70%).
Other sources of bone mets : thyroid, renal cell carcinoma, lung cancer, melanoma
Osteolytic :
Osteobastic:
Ignore breast in this list!
Breast cancer - The great majority of breast CA produces osteolytic bone lesions, osteoblastic areas are also usually present
Initially, bacilli enter macrophages and prevent formation of the phagolysosome. So they initially proliferate within macrophages.
Development of cell mediated immunity takes about 3 weeks.
Meningitis can be classified as acute, aseptic (viral) and chronic.
Chronic meningitis include Tuberculous, spirochetal and cryptococcal.
| Acute pyogenic meningitis | Aseptic meningitis | Chronic meningitis |
|---|---|---|
| Strep pneumoniae / Listeria | Viral | |
| Pus in subarachnoid space | No gross morphological changes | |
| Ventriculitis/ abscess formation | ||
| Abundant neutrophils in CSF; neurophils can completely fill the SA space | Mononuclear cells, not may neutrophils | |
| Neurologic symptoms are uncommon | Altered conciousness, coma, personality changes | |
| CN palsies are uncommon | Cranial nerve (II and VI) palsies | |
Neonates -> E coli.
Adolescents -> Neisseria meningitides
Older adults and elderly -> Streprococcus pneumoniae and Listeria monocytogenes.
Pus fills the subarachnoid space; it may invade the brain by tracking along veins in severe cases (or cause ventriculitis)
Clinical: subacute (few weeks) of headache, fever, vomiting, altered sensorium.
Cranial nerve palsies
Mononuclear cells present on CSF analysis.
Massively elevated CSF protein.
Can cause arachnoid fibrosis -> [[Neurology Miscellaneous#Subarachnoid space|hydrocephalus]].
subarachnoid space contains a gellatinous, fibrous exudate.
Microscopy: lymphocytes, macrophages, granulomas, caseous necrosis.
Obliterative endarteritis of vessels passing in the Subarachnoid space.
Hyponatremia is another complication.